State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Cell Mol Life Sci. 2019 May;76(9):1713-1727. doi: 10.1007/s00018-019-03022-7. Epub 2019 Jan 22.
Testicular tumors are the most common tumors in adolescent and young men and germ cell tumors (TGCTs) account for most of all testicular cancers. Increasing incidence of TGCTs among males provides strong motivation to understand its biological and genetic basis. Gains of chromosome arm 12p and aneuploidy are nearly universal in TGCTs, but TGCTs have low point mutation rate. It is thought that TGCTs develop from premalignant intratubular germ cell neoplasia that is believed to arise from the failure of normal maturation of gonocytes during fetal or postnatal development. Progression toward invasive TGCTs (seminoma and nonseminoma) then occurs after puberty. Both inherited genetic factors and environmental risk factors emerge as important contributors to TGCT susceptibility. Genome-wide association studies have so far identified more than 30 risk loci for TGCTs, suggesting that a polygenic model fits better with the genetic landscape of the disease. Despite high cure rates because of its particular sensitivity to platinum-based chemotherapy, exploration of mechanisms underlying the occurrence, progression, metastasis, recurrence, chemotherapeutic resistance, early diagnosis and optional clinical therapeutics without long-term side effects are urgently needed to reduce the cancer burden in this underserved age group. Herein, we present an up-to-date review on clinical challenges, origin and progression, risk factors, TGCT mouse models, serum diagnostic markers, resistance mechanisms, miRNA regulation, and database resources of TGCTs. We appeal that more attention should be paid to the basic research and clinical diagnosis and treatment of TGCTs.
睾丸肿瘤是青少年和年轻男性中最常见的肿瘤，生殖细胞肿瘤（TGCTs）占所有睾丸癌的大部分。男性 TGCTs 的发病率不断上升，这为了解其生物学和遗传基础提供了强有力的动力。染色体 12p 臂的增益和非整倍体几乎普遍存在于 TGCTs 中，但 TGCTs 的点突变率较低。人们认为 TGCTs 是从精原细胞瘤前体性小管内生殖细胞肿瘤发展而来的，这种肿瘤被认为是在胎儿或产后发育过程中，生殖细胞正常成熟失败而产生的。青春期后，侵袭性 TGCT（精原细胞瘤和非精原细胞瘤）就会发生进展。遗传因素和环境风险因素都被认为是 TGCT 易感性的重要因素。全基因组关联研究迄今为止已经确定了 30 多个 TGCT 风险位点，这表明多基因模型更符合该疾病的遗传特征。尽管由于其对铂类化疗的特殊敏感性，治愈率很高，但为了降低这个未得到充分治疗的年龄组的癌症负担，仍然迫切需要探索发生、进展、转移、复发、化疗耐药、早期诊断和无长期副作用的可选临床治疗的机制。本文对 TGCTs 的临床挑战、起源和进展、危险因素、TGCT 小鼠模型、血清诊断标志物、耐药机制、miRNA 调控和数据库资源进行了综述。我们呼吁更多地关注 TGCTs 的基础研究和临床诊断与治疗。
